4lko | pdb_00004lko

Crystal structure of human DPP-IV in complex with BMS-744891

spinqualitylabelsall models 4lko, resolution 2.43Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4lko is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.43Å Ligands: 1WH Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DPP4_HUMAN Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also regulates lymphocyte-epithelial cell adhesion. In association with FAP is involved in the pericellular proteolysis of the extracellular matrix (ECM), the migration and invasion of endothelial cells into the ECM. May be involved in the promotion of lymphatic endothelial cells adhesion, migration and tube formation. When overexpressed, enhanced cell proliferation, a process inhibited by GPC3. Acts also as a serine exopeptidase with a dipeptidyl peptidase activity that regulates various physiological processes by cleaving peptides in the circulation, including many chemokines, mitogenic growth factors, neuropeptides and peptide hormones. Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline. Publication Abstract from PubMed Optimization of a 5-oxopyrrolopyridine series based upon structure-activity relationships (SAR) developed from our previous efforts on a number of related bicyclic series yielded compound 2s (BMS-767778) with an overall activity, selectivity, efficacy, PK, and developability profile suitable for progression into the clinic. SAR in the series as well as characterization of 2s are described. Optimization of Activity, Selectivity, and Liability Profiles in 5-Oxopyrrolopyridine DPP4 Inhibitors leading to clinical candidate (Sa)-2-(3-(Aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]py ridin-6(7H)-yl)-N,N-dimethylacetamide (BMS-767778).,Devasthale P, Wang Y, Wang W, Fevig JM, Feng J, Wang A, Harrity T, Egan D, Morgan N, Cap M, Fura A, Klei H, Kish K, Weigelt C, Sun L, Levesque P, Moulin F, Li YX, Zahler R, Kirby M, Hamann LG J Med Chem. 2013 Aug 21. PMID:23964740 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dipeptidyl peptidase 3D structures

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